Abstract
In recent years, numerous pathways were explored in the pathogenesis of COPD in the quest for new potential therapeutic targets for more personalised medical care. In this context, the study of the cystic fibrosis transmembrane conductance regulator (CFTR) began to gain importance, especially since the advent of the new CFTR modulators which had the potential to correct this protein’s dysfunction in COPD. The CFTR is an ion transporter that regulates the hydration and viscosity of mucous secretions in the airway. Therefore, its abnormal function favours the accumulation of thicker and more viscous secretions, reduces the periciliary layer and mucociliary clearance, and produces inflammation in the airway, as a consequence of a bronchial infection by both bacteria and viruses. Identifying CFTR dysfunction in the context of COPD pathogenesis is key to fully understanding its role in the complex pathophysiology of COPD and the potential of the different therapeutic approaches proposed to overcome this dysfunction. In particular, the potential of the rehydration of mucus and the role of antioxidants and phosphodiesterase inhibitors should be discussed. Additionally, the modulatory drugs which enhance or restore decreased levels of the protein CFTR were recently described. In particular, two CFTR potentiators, ivacaftor and icenticaftor, were explored in COPD. The present review updated the pathophysiology of the complex role of CFTR in COPD and the therapeutic options which could be explored.
Highlights
Despite the considerable advances made in recent years, the mechanisms underlying the onset, pathogenesis and symptomatic development of chronic obstructive pulmonary disease (COPD) remain largely unknown
We aim to report the latest updates on the pathophysiology of CFTR in COPD and its possible treatments
In a murine animal model, some authors show that this treatment leads to an improvement by increasing the autophagy phenomena [62], which suggests a relevant role of this autophagy in the pathogenesis of COPD and its relationship with CFTR
Summary
Despite the considerable advances made in recent years, the mechanisms underlying the onset, pathogenesis and symptomatic development of chronic obstructive pulmonary disease (COPD) remain largely unknown. Biomedicines 2021, 9, 1437 oxidative and nitrosative stress, inflammatory mechanisms associated with alterations in innate and acquired immunity, and apoptosis or autoimmunity phenomena [6] Despite all these efforts, the factor which defines the patients who will develop COPD when exposed to tobacco still eludes us. Alterations in the functioning of this protein lead to no water being secreted into the bronchial mucus, transforming it into a dehydrated mucus, which is more viscous and, more resistant to the movement of the cilia and their physiological function, weakening this defence mechanism of the respiratory system This pathological condition is clearly seen in cystic fibrosis (CF) where there may be a complete absence of CFTR function [10]. We aim to report the latest updates on the pathophysiology of CFTR in COPD and its possible treatments
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have